The proposed research encompasses a detailed study of the physiological role of mitochondrial, pyridine nucleotide transhydrogenases in the essential process of anaerobic energy generation by the parasitic helminths. These enzymes act to link the critical utilization of substrate by the worm's mitochondria with succinate formation and ATP generation. It has become increasingly clear, that differences between host and parasite metabolic sequences allow for vulnerable sites for chemotherapeutic attack and disruption of parasite metabolism. Such differences are apparent in the worms' transhydrogenases when contrasted to corresponding mammalian systems. Thus the helminthic transhydrogenases would appear to be vulnerable sites and disruption of these systems would be expected to result in destruction of the parasites. The studies described involve a characterization of the metabolic import of the transhydrogenases and interactions of these inner membrane bound, mitochondrial enzymes with electron transport mechanisms using as the model system adult Hymenolepis diminuta. In addition, comparative studies will be undertaken to elucidate further the relationship of transhydrogenation and anaerobic phosphorylation in the helminths.